It is proposed to continue the sequential analysis of the induction of liver cancer with chemicals. Special emphasis will be given to two factors: the nature of the resistance to carcinogens induced by an initiating dose of a carcinogen; and, the creation of optimal conditions for selection of the initiated hepatocytes. In respect to the former, hepatocytes isolated from normal and carcinogen treated animals will be obtained by appropriate perfusion techniques. Measurement of activation and of uptake will be taken. With respect to the second, emphasis will be given to the further study of choline deficiency and the addition of methotrexate to the drinking water. Conditions for maximum selection will be developed.